How Frequently Should We Screen for Hepatitis C in US Hemodialysis Centers? Evaluating the Cost-Effectiveness of Different Strategies
Authors: Hanke Zheng, Eugene Lin
Journal: Journal of the American Society of Nephrology (2023)

Outbreaks of hepatitis C virus (HCV) among patients on hemodialysis resulted in calls for regular screening to prevent HCV infections. The Kidney Disease Improving Global Outcomes (KDIGO) released 2018 guidelines recommending regular HCV screening for patients receiving in-center dialysis: every 6 months for all in-center hemodialysis patients and every 1–3 months at centers with a detected case.1 Although laboratory costs are covered in the Medicare-bundled payment, frequent testing can become costly and inefficient, particularly because HCV outbreaks are rare in hemodialysis facilities. False positives can also result in avoidable health expenditures from unnecessary workup and treatments. An important question arises, is the marginal clinical benefit of performing additional HCV tests in chronic hemodialysis centers economically worthwhile? In this issue of JASN, Epstein et al.2 sought to answer this question. They assessed the cost-effectiveness of five different HCV screening strategies in US dialysis centers from a Medicare perspective over a 20-year time horizon: screening every 6 months as endorsed by the 2018 KDIGO guidelines, screening every year, screening every other year, screening once only at hemodialysis initiation, and no screening (the reference strategy). Cost-effectiveness was measured using the incremental cost-effectiveness ratio (ICER), which is the ratio of the difference in costs between two competing screening strategies and the difference in quality-adjusted life years (QALYs). One QALY is a year of perfect quality of life. For interpretation, the ICER compared two specific screening strategies and determines how much more costly one strategy is relative to the number of QALYs gained. The metric is the price of each additional year of perfect life that the screening strategy of interest provides Medicare. From the US health care sector perspective, $150,000/QALY is the recommended willingness-to-pay threshold.3 To estimate the ICER, the authors simulated the total cost of health care and the total QALYs over 20 years when using each strategy. They developed a microsimulation model that models HCV infections, liver disease progression, and HCV treatment for a hypothetical cohort of adults from a US hemodialysis population. The simulation accounted for dialysis center outbreaks, where more frequent screening more promptly truncates the transmission chain, shortening the outbreak. Calibration of the simulation model to national databases and the published literature closely approximated real-world circumstances. The model assessed total costs and QALY for each screening strategy and calculated ICERs from pairwise comparisons of strategies. Compared with a no screening strategy, screening only at hemodialysis initiation had an ICER of $82,793/QALY; screening every 2 years yielded an ICER of $140,193/QALY over screening only at hemodialysis initiation. The recommended KDIGO strategy of screening every 6 months had an ICER of $934,757/QALY over screening every 2 years, far more than $150,000/QALY, the US threshold for cost-effective interventions. To test the robustness of the conclusion, the authors performed extensive sensitivity analyses, including a probabilistic one that varies all key parameters simultaneously. Screening every 6 months was never cost-effective in all simulations under the conventional willingness-to-pay of $150,000/QALY. This study is the first to evaluate the cost-effectiveness of different HCV screening intervals among hemodialysis patients in the United States and provides meaningful evidence for the optimal strategy for payers and large hemodialysis centers. The investigation has several strengths. The calibrated model closely mirrors descriptions in the literature of the complex clinical progression of HCV infection and liver diseases for patients undergoing hemodialysis. In addition, concordance with national databases, such as the United States Renal Data System, enhances the plausibility and generalizability of the model. Furthermore, the findings are robust in a wide set of scenario and sensitivity analyses. The study showed that the KDIGO-recommended screening interval is likely not cost-effective compared with an extensive range of relaxed screening alternatives. Thus, guidelines should re-evaluate whether recommendations should be revised for dialysis facilities in the United States. Readers should recognize limitations of this study. First, uncertainty limits the model, especially because no randomized trials have identified the most efficacious strategy. Second, the authors extrapolated over a 20-year period; most studies do not provide empirical evidence over such a long timeframe. Third, models that simulate infectivity might exacerbate statistical errors, a parameter that is difficult to measure and subject to stochastic noise. Fourth, the investigation simulates behaviors during an HCV outbreak, and it is unclear whether facilities in the real world would respond to outcomes at the speed the authors modeled. Finally, the probabilistic-sensitivity analysis did not identify a dominant screening strategy from a cost-effectiveness standpoint. Still, the authors find that a more relaxed strategy of screening once only at dialysis initiation, screening every year, or screening every 2 years is very likely substantially more cost-effective than the KDIGO guideline of screening every 6 months. Underlying these results is the value of intense HCV screening in the hemodialysis population where the average life expectancy is 5–10 years.4 The likelihood of developing cirrhosis from HCV infection is low, and the progression is relatively slow—only 10%–20% of patients develop cirrhosis over 20–30 years of HCV infection, well over the average life span of patients on hemodialysis.5 In addition, the extremely high treatment costs for HCV and cirrhosis create a dilemma for policymakers and key stakeholders6 who must evaluate whether the cost of a stringent HCV screening strategy yields sufficient value from identifying HCV cases and outbreaks. Taken together, the KDIGO-endorsed HCV screening interval is not cost-effective from the Medicare perspective because of the high costs of implementation, downstream treatment for cirrhosis, and the limited gains in health benefits. Policymakers, payers, and dialysis providers should consider more conservative strategies that space out the interval of testing to either every 1 year or 2 years or once at the initiation of dialysis. Given the high cost of hemodialysis overall, opting for a more cost-effective HCV screening strategy may allow providers (particularly in safety-net settings) to prioritize higher-value care.